Obesity science & practice · 2023
Involvement of the vagus nerve in the anorectic effect of monoacylglycerol acyltransferase 2 inhibition in mice.
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Takemoto Kosuke, Kato Hideaki, Higashino Kenichi
Аннотация
BACKGROUND: Many of the drugs used for obesity treatment have adverse effects on the central nervous system. Therefore, novel treatments, such as peripherally acting drugs, are needed. Monoacylglycerol acyltransferase 2 (MGAT2), highly expressed in the small intestine, catalyzes the first step of triacylglycerol re-synthesis. MGAT2 inhibition suppresses food intake in high-fat diet (HFD)-fed mice, but the mechanisms remain unclear. Here, the involvement of the vagus nerve in MGAT2 inhibition-induced feeding suppression was investigated.
METHODS: Fasted mice were administered an MGAT2 inhibitor. Food intake was measured after HFD re-feeding, and the effect of capsaicin pretreatment on changes in food intake was evaluated. The number of c-fos-positive cells in the nucleus tractus solitarius and levels of appetite regulators were determined after HFD re-feeding or lipid gavage.
RESULTS: The anorectic effect of the MGAT2 inhibitor was abolished when vagus nerve function was interrupted by capsaicin. MGAT2 inhibition increased the number of c-fos-positive cells in the nucleus tractus solitarius and elevated intestinal oleoylethanolamide, plasma peptide tyrosine-tyrosine and plasma glucagon-like peptide-1 levels.
CONCLUSION: MGAT2 inhibition suppresses feeding behavior via peripheral vagus nerve signaling and may serve as a novel anti-obesity strategy with a low risk of unexpected central nervous system-related adverse effects.
METHODS: Fasted mice were administered an MGAT2 inhibitor. Food intake was measured after HFD re-feeding, and the effect of capsaicin pretreatment on changes in food intake was evaluated. The number of c-fos-positive cells in the nucleus tractus solitarius and levels of appetite regulators were determined after HFD re-feeding or lipid gavage.
RESULTS: The anorectic effect of the MGAT2 inhibitor was abolished when vagus nerve function was interrupted by capsaicin. MGAT2 inhibition increased the number of c-fos-positive cells in the nucleus tractus solitarius and elevated intestinal oleoylethanolamide, plasma peptide tyrosine-tyrosine and plasma glucagon-like peptide-1 levels.
CONCLUSION: MGAT2 inhibition suppresses feeding behavior via peripheral vagus nerve signaling and may serve as a novel anti-obesity strategy with a low risk of unexpected central nervous system-related adverse effects.